PURPOSE: Obesity is a global public health issue linked to worsened skin and subcutaneous tissue infections (SSTIs), complicating clinical management and increasing healthcare costs. This study aimed to evaluate obesity's influence on hospitalization duration, readmission rates, and healthcare costs among patients with SSTIs, with an emphasis on sex-specific patterns. PATIENTS AND METHODS: This retrospective cohort study analyzed data from South Korea's national healthcare database. The study population comprised adults hospitalized with SSTIs between 2015 and 2020. Obesity measures included body mass index (BMI) and waist circumference (WC), categorized by standard thresholds. Statistical analyses included Cox proportional hazards models for hospitalization duration, while multivariable logistic regression evaluated readmission risks. Healthcare costs were analyzed using generalized linear models, with sex-stratified analysis to examine clinical and economic outcome disparities. RESULTS: Male patients demonstrated an inverse relationship between BMI and hospitalization duration and costs, with minimal WC influence. Conversely, female patients exhibited positive associations between both obesity measures and hospitalization outcomes. SSTI-related readmissions within two years increased with rising BMI and WC across both sexes ( CONCLUSION: Obesity substantially impacts SSTI clinical severity and economic costs, with distinct sex-specific disparities. Implementing tailored antimicrobial regimens, weight management strategies, and sex-specific treatment protocols is essential for outcome optimization and cost reduction. Future research should prioritize sex-specific interventions and resource allocation strategies in SSTI management.